Experiments have been undertaken to answer two related questions: (1) What is there in common between the euphoric effect of morphine and the "rewarding" effect of some natural stimuli, brain electrical stimuli, and some central stimulants such as the amphetamines and concaine? (2) Is there a neurophysiological action that is common to these effects of neurons that may be constituents of a central, positively-reinforcing mechanism? In tests using the method fo intracerebral self-injection, evidence has been obtained that rats will self-administer morphine at hypothalamic and preoptic sites, the classical self-stimulation sites, but not at striatal sites, where density of opiate receptors is high. This suggests that morphine has a direct "rewarding" effect and that the neuronal substrate for it overlaps to some extent with that for slef-stimulation. In another experiment, evidence has been obtained that morphine injected in the vicinity of hypothalamic neurons that normally are inhibited during self-stimulation behavior produces a depression of the spontaneous rate. This indicates that there is a local, inhibitory action of morphine on a selected group of neurons identified with a central reinforcing mechanism. In a third experiment, a comparison is being made between the behavioral stimulant action of d-amphetamine and morphine in 30-day-old rats treated at days 3,5,7, and 9 after birth with 6-OHDA (200 micron g) injected into the ventricles. The stimulant action of d-amphetamine is blocked in most cases in the treated neonatals as compared withthe controls of the same age. The effect of morphine at 2.5 and 3.5 mg/kg i.p. on the controls is mostly depressing, whereas on the treated animals it is variable, and in several instances stimulant effects were observed. A dose of 1.25 mg/kg will be tested to find out whether stimulant effects can be obtained in controls, and what changes are produced by treatment neonatally. These experiments are continuing, both to solidify the evidence and to test for elimination of unwanted variables.